Roadmap Leads to Innovative Biomanufacturing Strategies

Fotografiche/Shutterstock.comThe Biomanufacturing Technology Roadmap, an industry-wide initiative to accelerate innovation in the biomanufacturing industry, was published by the BioPhorum Operations Group (BPOG) in July 2017 (1). The roadmap focuses on biomanufacturing strategy over a 10-year timeframe and defines the needs of, challenges to, and potential solutions for the industry. With a diverse pool of participants from industry, academia, and regulatory, the roadmap is the result of collaborative efforts.

BioPharm International interviewed three members of the steering committee that led the collaborative effort for the roadmap. Rajesh G. Beri is technical director R&D, biomanufacturing, Lonza; Morten Munk is global technology partner at NNE, a pharma engineering firm; and Bert Frohlich is an independent consultant who previously served as director of cell culture process development at Shire Pharmaceuticals.

Different perspectives

BioPharm: Why is it important to have the different sides of the industry represented in this collaboration?

Beri (Lonza): The biomanufacturing industry has responsibility to bring better, faster, cheaper, and higher quality therapeutics for serving patients. Biomanufacturers are uniquely aware of the challenges faced during development and manufacturing of biologics and they are in the best position to communicate their needs to the suppliers and academic community. It is therefore important to have biomanufacturers involved in [this] collaboration.

In addition, academia plays a key role in conducting fundamental research and pioneering new technologies; suppliers develop and commercialize new technologies; and regulators ensure that new advancements conform to existing guidelines or develop new guidelines in collaboration with industry, if required. Thus it is important to have all four stakeholders involved in the development of the roadmap.

Munk (NNE): I believe all groups have the same common goal, which is to make safe and efficient pharmaceutical available for the patients. The best way to do this, is through collaboration and knowledge sharing. Moreover, the different groups (biomanufacturer, supplier, academia, and regulators) have different perspectives and focus areas in their effort to meet this common goal. Thus, it is important for each group to better understand the perspective of the other groups, and this is best done through dialog and working together on concrete projects.

Frohlich: The initiative started off as a consortium of only major biomanufacturers. More recently, supplier companies and academic institutions have joined. This staged integration was very much the right approach since it was the first time the biopharmaceutical industry came together to collaborate in the pre-competitive space. It took some time for the biomanufacturing community to learn the rules of engagement and to set a common direction.

These companies had the most experience in the direct supply of drug to patients. It was clear from the beginning that the full benefit of the roadmap would eventually only be realized with the participation of the whole biopharma industry, including the supplier community and academia. However, the manufacturers needed some time to speak with one voice and to articulate a vision. Until that point, each company spoke directly to suppliers and academic collaborators individually. Consequently, these supporting communities often received very different messages from many different companies.

To find solutions to current obstacles, engaging the supplier community is of key importance especially in more mature technologies that are closer to commercial viability. Likewise, engaging the academic community is key in terms of building a future workforce as well as attacking newer, more novel technologies and applications. By indicating the major and most urgent obstacles to progress in the biopharmaceutical industry through the roadmap, suppliers and academic labs can pursue solutions with greater certainty that what they develop will serve an important need.

Also, right from the beginning, it was realized that the regulatory community should also be engaged at some point and even that the various regulatory agencies should be seen as partners to the evolving roadmap. As a regulated industry, any solution will have to meet regulatory approval before it can be implemented.

Roadmap benefits

BioPharm: What are the major benefits of this roadmap?

Beri (Lonza): As mentioned previously, biomanufacturers have collectively contributed their challenges and needs and these have been documented in the roadmap. In addition, an assessment was performed with the suppliers and academics to estimate the time required to develop technologies addressing the needs and challenges. Thus, biomanufacturers can use these documented exercises to project availability of newer technologies and determine evaluation/implementation plans for their facilities.

Separately, 12 individual projects have been launched addressing the critical needs selected by member companies. By actively participating in these project teams, biomanufacturers can contribute to project success.

Munk (NNE): The pharma industry is a conservative industry, and very few dare to be the first movers in exploring new technology. The Biomanufacturing Technology Roadmap offers a forum for the “brave” and forward-looking to share experiences and results in their work with innovation. This helps all members to make better business cases in their individual companies.

For example, when presenting a new idea, the first questions quite often are: Who else have tried this? What is the risk? How will the regulatory bodies view this? Through the collaboration in BPOG, it is a lot easier to give convincing answers to such questions. Furthermore, I find it inspiring that members of BPOG have the same passion, drive, and courage as I do to try to make a difference in our industry.

Frohlich: The mapping process began with the identification of the major business drivers facing the biopharma industry: speed, flexibility, cost, and quality. The map then was designed to target these drivers using various metrics. While the most relevant metrics are still evolving, they will be useful in identifying specific deficiencies and eventually estimating and realizing the value of a solution.

More importantly, however, is the intrinsic value in a collaborative approach. It is becoming increasingly clear that the cost of progressing various technologies and industry standards is less costly if done collectively than if pursued individually by companies.

The focus of the Biomanufacturing Technology Roadmap is on the chemistry, manufacturing, and controls (CMC) side of drug commercialization. For most companies, CMC-based technologies are not differentiating and do not impinge on product or therapeutic intellectual property. The cost of supplying a drug to market is appreciable, and the gain from collaboration in the pre-competitive space is likely to outweigh the apparent competitive advantage of keeping certain practices and technologies proprietary.

Furthermore, there is greater certainty within any organization in pursuing a given direction if it has been vetted with industry colleagues. The roadmap can even help a practitioner convince his or her senior management of the benefits of investing in certain approaches and technologies and at lower risk.

Evolving capacity needs

BioPharm: How would the Biomanufacturing Technology Roadmap remain relevant as the manufacturing technology and capacity needs in the biopharmaceuticals industry continue to evolve, for example, with precision medicines?

Beri (Lonza): Fairly early in the roadmapping process, we tackled the anticipated manufacturing scenarios. One of the manufacturing scenarios we determined would be increasingly relevant was mobile and modular facilities. Such smaller scale and portable facilities will increasingly gain importance for delivering precision medicines of tomorrow. In addition, there is ongoing discussion in the BPOG Technology Roadmapping Steering Committee of developing a roadmap with newer biologic modalities, such as gene therapy. Thus, the roadmap will continue to be updated in order to deal with the continuous evolution of the biopharmaceutical industry.

Munk (NNE): We are in the middle of a paradigm shift, where the distance between the manufacturers and the patient will get shorter and shorter. Individual patient needs and considerations are going to affect the way pharmaceuticals are produced, shipped, and administrated. Closer collaboration between biomanufacturers, suppliers, academia, and regulators are pivotal to fully understand those needs and find the best solutions for how challenges can be met, while still keeping the treatment affordable. BPOG offers a forum to share knowledge of how to incorporate the patient perspective in the way the future pharmaceuticals are delivered to the patient.

Frohlich: By definition, a roadmap is forward-looking. It attempts to predict future needs from current trends and obstacles. Additionally, the Biomanufacturing Technology Roadmap should be viewed as a dynamic tool and not a static map. By refreshing the roadmap periodically, its direction will evolve with the industry.

By necessity, the roadmap scope had to be restricted initially. Due to resource limitations within the member companies and BPOG and a lack of expertise in some of the newer biopharmaceutical products and treatment modalities, the first edition of the map could not be all-encompassing. The initial emphasis of the Biomanufacturing Technology Roadmap has been on the manufacture of recombinant proteins and, even more specifically, on monoclonal antibodies (mAbs).

With successive editions of the roadmap, other industry sectors will be addressed. As new therapeutic technologies continue to emerge, the required production technologies will need to be included. To some degree, the need for flexibility in facility design has already been realized. Future facilities will need to accommodate an increasingly wider array of product types to justify the significant capital investments associated with manufacturing capacity.

It is also important to note that the vision of the roadmap is not to be redundant with other industry initiatives but to be complementary. Its role should be viewed as having a coordinating function within the industry as a whole.

For example, the cell therapy sector has already begun its own map; the Biomanufacturing Technology Roadmap would not attempt to repeat or supersede the cell therapy map, but to incorporate what has already been addressed.

Also, many aspects of the Biomanufacturing Technology Roadmap are not specific to any specific manufacturing platform. Issues such as automation standards, supplier partnerships, knowledge management, and new paradigms for real-time release will be of general use and applicability to the industry.

Furthermore, all outputs of the BPOG Biomanufacturing Technology Roadmap will be published to a public forum, and the steering committee is committed to taking input from smaller players and the industry at large.

Regulatory alignment

BioPharm: How would the Biomanufacturing Technology Roadmap help biomanufacturers align with regulatory standards?

Beri (Lonza): The regulatory manufacturing standards will continue to dictate biomanufacturing practices, so any new technologies will have to conform to the standards. However, newer standards may be required due to transformational changes likely to be brought in the move to full digitalization, big data analysis, machine intelligence, etc. Biomanufacturers can thus play a key role in advising regulatory agencies for requiring new standards or guidelines.

Munk (NNE): This most import task for the regulators is to assess risk in the broadest perspective. This consideration is best supported from the industry, by addressing the regulators with a common voice, and presented through risk assessments based on a broad perspective from a wide range of players in the field.

This helps the regulators to better understand and evaluate the risk benefit profile of new technologies, leading to an easier path and faster acceptance of improvements in biopharmaceutical manufacturing.

Frohlich: As mentioned previously, engaging with regulators at the earliest formation of the roadmap was seen as a critical component. In fact, a ‘regulatory’ sub-team has already been formed, and some informal communication with FDA has begun.

The intention is to keep the agencies informed of the Biomanufacturing Technology Roadmap progress, if not seek their direct input. This is a global effort and thus other national and international jurisdictions will be brought in. For example, there is already a desire to make progress in certain workstreams so that they will be in a position to influence new guidance documents expected from the International Council for Harmonization.

The chief benefit of the roadmap to the industry as a whole is that regulators will hear a single common voice with regard to needs and concerns. Conversely, the industry will hear and interpret the response from the health authorities in a collective manner.

In the prior paradigm, each company asked for advice and each would interpret the advice and/or requirements on their own. It is no wonder that companies seek to comply with the same regulations in very different ways.

Success stories

BioPharm: The first edition of BPOG’s Biomanufacturing Technology Roadmap was just recently published, but are there any existing scenarios or case studies among the members where this collaboration has already worked, aka, a success story that you can share?

Munk (NNE): Several of the member companies have told me that they use the roadmap in their internal strategic technology evaluation work, and the experience and guidance shared in the document helps them to sharpen their development efforts. Furthermore, it is also my understanding that the document and, maybe even to a large degree the network within BPOG, helps the innovation champions of the individual companies to push their organizations a bit more in the right direction to dare to give new technology a chance.

All new technology initiatives have initial challenges and setbacks, which are difficult to get over, but it helps if it is possible to use experiences from other companies on how they overcame those roadblocks and managed to lead the projects to a successful outcome.

Frohlich: The first edition of the BPOG Biomanufacturing Technology Roadmap is already showing some progress and impact in simply acknowledging the need for some standardization in the industry. While this is not a new idea, particularly around single-use equipment and components and in data structures and automation, there is a greater recognition and agreement that these areas should be addressed.

Again, the goal of the roadmap is not to supersede other industry initiatives but to somehow tie them together.

Another initial success is in BPOG’s official engagement with a US public-private consortium. An agreement recently signed with The National Institute for Innovation in Manufacturing Biopharmaceuticals will tie in their vision of the future as well as harness their resources (2).

Such partnerships underscore the mission of the roadmap not to dictate solutions or be redundant with academic pursuits, but rather to inform and collaborate, thereby helping guide the industry forward as a whole and all its players to achieve greater efficiency in supplying drug to patients worldwide.